Linux kernel seems to be the common thread, however, another Linux machine that I have still works fine with Signet, even though it's running a very recent kernel.
This makes me think that the problem is some kernel configuration option that is only enabled in security hardened systems. So this is the lead I will follow.
/me rolls up sleeves
Welp, time to dig into USB packet sniffing...
https://docs.kernel.org/5.10/usb/usbmon.html
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OK, sniffing USB packets is pretty cool, albeit noisy AF!